An Open-Label Study Comparing Glofitamab and Polatuzumab Vedotin + Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma

Purpose

The purpose of this study is to compare the efficacy and safety of glofitamab in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs Pola-R-CHP in participants with previously untreated CD20-positive large B-cell lymphoma (LBCL).

Condition

  • Large B-Cell Lymphoma

Eligibility

Eligible Ages
Between 18 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Previously untreated participants with CD20-positive LBCL - Ability to provide tumor tissue - International prognostic index (IPI) score 2-5 - Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2 - At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or MRI - Left ventricular ejection fraction (LVEF) >/=50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO) - Adequate hematologic function - Negative HIV test at screening with exceptions as defined by the protocol - Negative SARS-CoV-2 antigen or PCR test

Exclusion Criteria

  • Contraindication to any of the individual components of Pola-R-CHP or glofitamab, including prior receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products - Prior solid organ transplantation - Participants receiving systemic immunosuppressive agent such as, but not limited to cyclosporin, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 4 weeks prior to first dose of study treatment - Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease - History of indolent lymphoma (e.g., Follicular Lymphoma, Marginal Zone Lymphoma, Waldenstrom macroglobulinemia) - Current diagnosis of the following: Follicular lymphoma grade 3B; transformations of indolent B-cell lymphomas (e.g., de novo transformed follicular lymphoma); mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; primary large B-cell lymphoma of immune-privileged sites (encompassing primary diffuse large B-cell lymphoma of the CNS, primary large B-cell lymphoma of the vitreoretina and primary large B-cell lymphoma of the testis); primary effusion DLBCL; and primary cutaneous DLBCL, leg type - Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma - Prior treatment with systemic immunotherapeutic agents - Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of Cycle 1 - Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of Cycle 1 - Prior radiotherapy to the mediastinal/pericardial region - Prior therapy for LBCL, with the exception of corticosteriods - Corticosteroid use > 30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control - History of other malignant or non-malignant diseases that could affect compliance with the protocol or interpretation of results - Significant or extensive history of cardiovascular disease - Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis - Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease - Known or suspected chronic active Epstein-Barr viral infection - Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) - Active autoimmune disease requiring treatment - Clinically significant liver disease - Live, attenuated vaccine within 4 weeks before study treatment infusion on Day 1 of Cycle 1 or anticipation that such a live, attenuated vaccine will be required during the study. Live vaccines during the study and until participants B cells recover are prohibited - Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety - Suspected active or latent tuberculosis - Positive test results for chronic hepatitis B infection, hepatitis C, or the human T-lymphotropic virus type 1 (HTLV-1) - History of progressive multifocal leukoencephalopathy

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Glofitamab + Pola-R-CHP 		Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).
  • Drug: Glofitamab
    Participants will receive intravenous (IV) glofitamab
  • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin in combination with R-CHP
  • Drug: Rituximab
    Participants will receive IV rituximab
  • Drug: Cyclophosphamide
    Participants will receive cyclophosphamide as part of CHP chemotherapy
  • Drug: Doxorubicin
    Participants will receive IV doxorubicin
  • Drug: Prednisone
    Participants will receive oral prednisone as part of CHP chemotherapy
Active Comparator
Pola-R-CHP 		Participants will receive Pola-R-CHP.
  • Drug: Glofitamab
    Participants will receive intravenous (IV) glofitamab
  • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin in combination with R-CHP
  • Drug: Rituximab
    Participants will receive IV rituximab
  • Drug: Cyclophosphamide
    Participants will receive cyclophosphamide as part of CHP chemotherapy
  • Drug: Doxorubicin
    Participants will receive IV doxorubicin
  • Drug: Prednisone
    Participants will receive oral prednisone as part of CHP chemotherapy

Recruiting Locations

Medstar Franklin Square Medical Center
Baltimore, Maryland 21237

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GO44145 https://forpatients.roche.com/
888-662-6728
global-roche-genentech-trials@gene.com